Polymorphonuclear leukocytes (PMNs) play a major role as a front-line antibacterial defense system and they are consistently found in crevicular exudates from periodontal patients. It is likely that PMNs play a critical role in protecting the host against microbial attack in this area. It is conceivable that specific pathogenic plaque bacteria perturb the PMN system and thereby gain an advantage over the host. Elevated numbers of spirochetes are consistently found in plaque samples from periodontal patients, suggesting an active role for these organisms in the development of periodontal disease but detailed information on PMN-spirochets interactions in meager. In order to address such issues the following studies are proposed: 1. To determine if plaque spirochetes modulate PMN functions. Various species of oral spirochetes will be incubated with PMNs in vitro. PMN responses (including chemotaxis, phagocytosis, oxygen metabolism, lysosomal degranulation etc.) will then be recorded. PMNs will also be preincubated with spirochetes to determine the effect of such interaction of PMN responsiveness to secondary stimulants. 2. To characterize the mechanisms whereby spirochetes affect PMN functions. It is unclear how spirochetes modulate PMN functions on a molecular level. Spirochete-PMN interactions will be evaluated by monitoring intracellular activation and signal transduction (including cAMP conc,. Protein Kinase C activity, Calcium conc, etc). 3. To identify and isolate spirochete factors which perturb PMN functions. Conventional biochemical methods combined with monoclonal antibody techniques will be utilized to purify and characterize these factors. Studies on the cell biology of PMN-spirochete interactions will provide valuable information as to how spirochetes modulate PMN functions and will contribute to our understanding of the nature and consequences of these interactions in the development of periodontal disease.